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- Wang, Longwei, et al.
(författare)
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A Molybdenum Disulfide Nanozyme with Charge-Enhanced Activity for Ultrasound-Mediated Cascade-Catalytic Tumor Ferroptosis
- 2023
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Ingår i: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 62:11
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Tidskriftsartikel (refereegranskat)abstract
- The deficient catalytic activity of nanozymes and insufficient endogenous H2O2 in the tumor microenvironment (TME) are major obstacles for nanozyme-mediated catalytic tumor therapy. Since electron transfer is the basic essence of catalysis-mediated redox reactions, we explored the contributing factors of enzymatic activity based on positive and negative charges, which are experimentally and theoretically demonstrated to enhance the peroxidase (POD)-like activity of a MoS2 nanozyme. Hence, an acidic tumor microenvironment-responsive and ultrasound-mediated cascade nanocatalyst (BTO/MoS2@CA) is presented that is made from few-layer MoS2 nanosheets grown on the surface of piezoelectric tetragonal barium titanate (T-BTO) and modified with pH-responsive cinnamaldehyde (CA). The integration of pH-responsive CA-mediated H2O2 self-supply, ultrasound-mediated charge-enhanced enzymatic activity, and glutathione (GSH) depletion enables out-of-balance redox homeostasis, leading to effective tumor ferroptosis with minimal side effects.
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- Wan, Lu Ming, et al.
(författare)
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Heparanase Facilitates PMA-Induced Megakaryocytic Differentiation in K562 Cells via Interleukin 6/STAT3 Pathway
- 2020
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Ingår i: Thrombosis and Haemostasis. - : GEORG THIEME VERLAG KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 647-657
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase (HPSE) is an endo-beta-D-glucuronidase that cleaves heparan sulfate and hence participates in remodeling of the extracellular matrix, leading to release of cytokines that are immobilized by binding to heparan sulfate proteoglycans (HSPGs), and consequently activating signaling pathways. This function of HPSE is correlated to its expression level that is normally very low in majority of the tissues. Exceptionally, human platelets express high level of HPSE, suggesting a unique physiological role in this cell. Using K562 cell line, we found a progressive increase of HPSE during the megakaryocytic differentiation. Analysis of a series of megakaryocytic differentiation-related heparin-binding proteins (HBPs) in the cell culture medium revealed an exclusive positive correlation between the level of interleukin 6 (IL-6) and HPSE expression. IL-6 modulated megakaryocytic differentiation through activation of STAT3. Further, we demonstrated that overexpression of HPSE potentiates megakaryocytic differentiation, whereas elimination of HPSE led to a delayed differentiation. This function of HPSE is associated with its activity, as overexpression of inactive HPSE had no effect on IL-6 production and megakaryocytic differentiation. The role of HPSE is further supported by the observation in an umbilical cord blood CD34+ cells megakaryocytic differentiation model. Our data propose a novel role for HPSE in platelets production by a HPSE/IL-6/STAT3 positive feedback loop that specifically regulates megakaryocytes maturation.
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- Zheng, Fenglian, et al.
(författare)
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Structural and functional hippocampal alterations in Multiple sclerosis and neuromyelitis optica spectrum disorder
- 2022
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 28:5, s. 707-717
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Objective: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. Methods: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. Results: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). Conclusions: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.
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- Cheng, Yirui, et al.
(författare)
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NDFIP1 limits cellular TAZ accumulation via exosomal sorting to inhibit NSCLC proliferation
- 2023
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Ingår i: Protein & Cell. - : Springer Nature. - 1674-800X .- 1674-8018. ; 14:2, s. 123-136
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Tidskriftsartikel (refereegranskat)abstract
- NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
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- Wu, Shi-Xun, et al.
(författare)
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Expression profiles of genes involved in apoptosis and selenium metabolism in articular cartilage of patients with Kashin-Beck osteoarthritis.
- 2014
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Ingår i: Gene. - : Elsevier. - 0378-1119 .- 1879-0038. ; 535:2, s. 124-130
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Tidskriftsartikel (refereegranskat)abstract
- Kashin-Beck disease (KBD) is a special type of endemic osteoarthritis. It has been suggested that alterations in selenium metabolism and apoptosis play a role in KBD. However, the underlying molecular mechanism remains largely unclear. We performed a microarray analysis using RNA isolated from cartilages of KBD patients and healthy controls, through Significance Analysis of Microarray (SAM) software. Functional gene networks and crucial molecules associated with differentially expressed genes were investigated via Ingenuity Pathway Analysis (IPA) and hub gene analysis. Quantitative real-time PCR was used to check the validation of chip test. We identified 52 up-regulated apoptosis-related genes and 26 down-regulated selenium-related genes between KBD and controls, and these genes associated with the "MYC-mediated apoptosis signaling pathway". We confirmed the results from array studies with quantitative real-time PCR analysis. Our results suggest that abnormal regulation of selenium metabolism and apoptosis through the MYC mediated signaling pathway contributes to the pathogenesis of KBD, but the relationship between apoptosis gene and selenium gene was not found.
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- Zhuo, Lang, et al.
(författare)
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Time Trade-Off Value Set for EQ-5D-3L Based on a Nationally Representative Chinese Population Survey
- 2018
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Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 21:11, s. 1330-1337
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To obtain a nationally representative Chinese three-level EuroQol five-dimensional questionnaire value set based on the time trade-off (TTO) method.Methods: A multistage, stratified, clustered random nationally representative Chinese sample was used. The study design followed an adapted UK Measurement and Valuation of Health protocol. Each respondent valued 11 random states plus state 33333 and "unconscious" using the TTO method in face-to-face interviews. Three types of models were explored: ordinary least squares, general least squares, and weighted least squares models.Results: In total, 5939 inhabitants aged 15 years and older were interviewed. Of these, 5503 satisfactorily interviewed participants were included in constructing models. An ordinary least squares model including 10 dummies without constant and N3 had a mean absolute error of 0.083 and a correlation coefficient of 0.899 between the predicted and mean values. Goodness-of-fit indices of two models based on split subsample were similar.Conclusions: TTO values were higher in our study compared with those in a study carried out in urban areas, which is mirrored by the higher values in rural areas. Several other aspects, in addition to the valuation procedure, might have influenced the results, such as factors beyond demographic factors such as view on life and death and believing in an afterlife, which need further investigation. Future studies using the three-level EuroQol five-dimensional questionnaire should consider using this value set based on a nationally representative sample of the Chinese population.
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- Eriksson, Kimmo, et al.
(författare)
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Perceptions of the appropriate response to norm violation in 57 societies
- 2021
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Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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| 10. |
- Jin, Ying, et al.
(författare)
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"Soap bubble" sign as an imaging marker for posterior fossa ependymoma Group B
- 2023
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 65, s. 1707-1714
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the predictive value of the "soap bubble" sign on molecular subtypes (Group A [PFA] and Group B [PFB]) of posterior fossa ependymomas (PF-EPNs).Methods: MRI scans of 227 PF-EPNs (internal retrospective discovery set) were evaluated by two independent neuroradiologists to assess the "soap bubble" sign, which was defined as clusters of cysts of various sizes that look like "soap bubbles" on T2-weighted images. Two independent cohorts (external validation set [n = 31] and prospective validation set [n = 27]) were collected to validate the "soap bubble" sign.Results: Across three datasets, the "soap bubble" sign was observed in 21 PFB cases (7.4% [21/285] of PF-EPNs and 12.9% [21/163] of PFB); none in PFA. Analysis of the internal retrospective discovery set demonstrated substantial interrater agreement (1st Rating: kappa = 0.71 [0.53-0.90], 2nd Rating: kappa = 0.83 [0.68-0.98]) and intrarater agreement (Rater 1: kappa = 0.73 [0.55-0.91], Rater 2: kappa = 0.74 [0.55-0.92]) for the "soap bubble" sign; all 13 cases positive for the "soap bubble" sign were PFB (p = 0.002; positive predictive value [PPV] = 100%, negative predictive value [NPV] = 44%, sensitivity = 10%, specificity = 100%). The findings from the external validation set and the prospective validation set were similar, all cases positive for the "soap bubble" sign were PFB (p < 0.001; PPV = 100%).Conclusion: The "soap bubble" sign represents a highly specific imaging marker for the PFB molecular subtype of PF-EPNs.
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